The La antigen is an abundant nuclear protein recognized by sera from patients with autoimmune disease (systemic lupus erythrematosus or Sjogren's syndrome). The antigen is transiently bound by essentially all the RNAs transcribed by RNA polymerase III (class III RNAs) including the virally-encoded VA and EBER RNAs and the precursors of tRNAs, 5S rRNA, and 7SL RNA. Its conservation across vertebrate species, abundance, and ubiquitous association with RNAs of this class suggest the protein plays a pivotal role in their biogenesis. The long term goal of this project is to understand factors which influence the expression of class III RNAs as they relate to cell growth and development. This proposed research will specifically analyze the role of the La protein in the biogenesis of class III RNAs. Several potential roles for the antigen in RNA processing and transport will be tested, including the possibilities that La stimulates processing, retains immature RNAs within the nucleus, or transports RNAs within the cell for their maturation or assembly into functional complexes. These roles will be tested by inactivating the antigen in oocytes of the clawed toad, Xenopus laevis, and analyzing the effect upon the processing and intracellular fate of microinjected class III RNA precursors. Elucidation of the role of La in class III gene expression will produce a greater understanding of class III expression as well as possible insights into the strategies used by viral pathogens to recruit host functions. Moreover, the RNA binding associated with La function, like that of other lupus antigens involved in RNA processing, may contribute to its inappropriate recognition by the immune system in pathology. Determination of the role of La may have significant implications for the understanding of the molecular etiology of autoimmune disease.